The ordered structure of cartilage is in part dependent on the physical-chemical properties of its proteoglycans. Some human genetic bone dysplasias may reflect mutation that result in the synthesis of structurally defective proteoglycans. It has not been possible to examine this question because reliable methods have not been established for the culture of human chondrocytes. The objectives of this research are: (1) to develop methods for the culture of human chondrocytes which maintain the chondrocyte phenotype in-vitro, (2) study selected parameters of proteoglycan metabolism and structure to establish normative data and (3) compare the metabolism and structure of proteoglycans produced by normal chondrocytes to chondrocytes obtained from patients with genetic bone dysplasias to determine whether abnormalities in proteoglycan metabolism are the basis of their disease. Tissue cultures of chondrocytes will be studied and the proteoglycans synthesized by the cells characterized for their chemical composition, size and their functional integrity utilizing ultracentrifugation, column chromatography coupled to digestion with specific enzymes that free specific components of this complex molecule for detailed analyses.